Premium
Historical and methodological developments in clinical trials at the national cancer institute
Author(s) -
Gehan Edmund A.,
Schneiderman Marvin A.
Publication year - 1990
Publication title -
statistics in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.996
H-Index - 183
eISSN - 1097-0258
pISSN - 0277-6715
DOI - 10.1002/sim.4780090803
Subject(s) - clinical trial , medicine , randomization , randomized controlled trial , cancer
The first randomized clinical trial at the National Cancer Institute (NCI), planned in 1954, commenced in 1955 for the treatment of patients with acute leukaemia. The programme in clinical trials at NCI had strong influence from the clinician and administrator, C. Gordon Zubrod, who introduced the randomized clinical trial at NCI and organized the co‐operative clinical trials programme of the Cancer Chemotherapy National Service Center (CCNSC) beginning about 1955. The biostatistician, Marvin Schneiderman, collaborated on the first randomized trials in acute leukaemia and solid tumours and recruited the biostatisticians and statistical centres in the early phase of the co‐operative clinical trials programme of the CCNSC. From the beginning, there was acceptance of the principles of the randomization of patients and the statistical analysis of data. The sequence of clinical trials for a new agent included the non‐randomized phase I (dosage finding) and phase II (preliminary efficacy) trials as well as the phase III (comparison of treatments) trials. New concepts for the treatment of patients developed from 1955 to the mid‐1960s included the combination of therapies with independent activity to increase response rates and the administration of therapy to patients in a disease‐free (remission) state to prolong the disease‐free state. Methodological developments related to clinical trials up to the mid‐1960s included: a plan for phase II trials (Gehan 10 ); a generalization of the Wilcoxon test for the comparison of survival distributions with right‐censored data (Gehan 25 ); a test of proportional hazards for survival distributions, which later became known as the Mantel‐Haenszel test (Mantel 38 ), and an exponential regression model with an explanatory variable (Feigl and Zelen 41 ).